Working Paper Article Version 1 This version is not peer-reviewed

The PDZ-binding Motif of SARS-CoV Envelope Protein Induces Cancerization and Poor Prognosis of Lung Adenocarcinoma

Version 1 : Received: 11 March 2020 / Approved: 12 March 2020 / Online: 12 March 2020 (09:28:43 CET)

How to cite: Chen, L.; Zhong, L. The PDZ-binding Motif of SARS-CoV Envelope Protein Induces Cancerization and Poor Prognosis of Lung Adenocarcinoma. Preprints 2020, 2020030209 Chen, L.; Zhong, L. The PDZ-binding Motif of SARS-CoV Envelope Protein Induces Cancerization and Poor Prognosis of Lung Adenocarcinoma. Preprints 2020, 2020030209

Abstract

Both in lung adenocarcinoma (LUAD) and severe acute respiratory syndromes (SARS) uncontrolled inflammation could be detected in lung tissue. Whether the similarity mechanism exists is still unknown. PDZ-binding motif (PBM) in SARS-CoV E protein has been demonstrated as virulence factor induce inflammation storm. Study function of PBM in LUAD is significant for mechanism exploration of carcinogenesis mediated by SARS-CoV. To identify gene expression fluctuation induced by PBM, a microarray sequencing data of lung tissue infected by wild type (SARS-CoV-E-wt) and recombinant virus (SARS-CoV-E-mutPBM) was analysis followed by functional enrichment analysis. To understand the role of screened specific genes in LUAD, overall survival and immune correlation were calculated. A total of 12 genes (MAPK1, PRKCA, FGFR4, KDR, PTPRD, BCL2L15, UBD, MAMDC2, LTBP4, PTPRB, LGI3 and ITGA8) might participate in initial and development stage of LUAD through expression variation and mutation. Meanwhile, a total of 12 genes (CARHSP1, EIF4E2, HMGA1, IL1R2, MAGOHB, PVR, ADCY9, ELF5, ESYT3, SCML4, SECL14L4 and THRA) could lead to poorer prognosis via dysregulation. In addition, MAMDC2 and ITGA8 down-regulated by PBM could also alter prognosis. Though the conservative PBM (-D-L-L-V-) could be found at the end of carboxyl terminal in multi E proteins of coronaviruses, the specific function of each one depend on the whole amino acid sequence simultaneously. In conclusion, PBM of SARS-CoV E protein could promote carcinogenesis of LUAD by dysregulating important gene expression profiles followed by influence immune response and overall prognosis. The results in present study also provided reference for the therapy of SARS-CoV-2 in LUAD patients.

Subject Areas

SARS-CoV; PBM; envelope protein; LUAD; bioinformatics

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